Acetic Acid → HCID 178521029, compound

HRID 931279Notes

Reaction equation

HRID 931279 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[N:8]=[C:7]([C:9](=[NH:13])OCC)[CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.Cl.Cl.N[C:26]1[C:31]([NH2:32])=[CH:30][N:29]=[C:28]([N:33]2[CH2:38][CH2:37][CH2:36][C@@H:35]([C:39]([N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)=[O:40])[CH2:34]2)[N:27]=1.C(O)(=O)C>C(O)C>[N:41]1([C:39]([C@@H:35]2[CH2:36][CH2:37][CH2:38][N:33]([C:28]3[N:27]=[C:26]4[C:31]([N:32]=[C:9]([C:7]5[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:14])[F:15])[N:8]=5)[NH:13]4)=[CH:30][N:29]=3)[CH2:34]2)=[O:40])[CH2:42][CH2:43][CH2:44][CH2:45]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 89853293(R)-(1(4,5-Diaminopyrimidin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochlorideHCID 89853792Ethyl 6-(trifluoromethyl)picolinimidate

Product 1

HCID 178521029HCID 178521029, compoundYield 22.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
120 °C

Procedure

To a solution of ethyl 6-(trifluoromethyl)picolinimidate (291 mg, 1.3 mmol) and triethylamine (0.6 mL, 4.4 mmol) in ethanol (5 mL) was added dropwise a solution of (R)-(1-(4,5-diaminopyrimidin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (400 mg, 1.1 mmol) and acetic acid (0.3 mL, 6.6 mmol) in ethanol (10 mL) at room temperature over a period of 10 min. The reaction mixture was stirred for 16 h at 120° C. The mixture was concentrated and the residue was partitioned between ethyl acetate and water. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via preparative TLC to afford the title compound (110 mg, 20%). 1H NMR (400 MHz, DMSO-d6) δ 1.18-1.32 (m, 1H), 1.48 (d, 1H), 1.71 (t, 2H), 1.76-1.83 (m, 2H), 1.89 (dt, 3H), 2.55-2.64 (m, 2H), 2.85-3.03 (m, 2H), 3.42-3.50 (m, 1H), 3.51-3.63 (m, 1H), 4.76 (d, 2H), 8.00 (d, 1H), 8.22-8.32 (m, 1H), 8.49 (d, 1H), 8.83 (br s, 1H), 13.41 (br s, 1H). MS (ES+) (M+H) 446.33; LCMS retention time 3.34 min (Method S).

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified via preparative TLC

Sources & evidence

ORD record
ord-8474375c789747609fe328490337e860
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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